Abstract
In contrast with electrophilic enzyme-catalysed cyclisations in terpenoid biosynthesis, cyclisations of tetrahydrofuran moieties found in several groups of natural products, such as annonaceous acetogenins, neurofurans and phytooxylipins, appear to proceed through a nucleophilic cascade mechanism starting from bis-epoxy fatty acid precursors. This hypothesis was verified by epoxide-hydrolase-catalysed hydrolytic ring-opening/cyclisation cascades starting from a methylene-interrupted meso-bis-epoxide model substrate, which furnished the corresponding THF products with excellent de and ee values. Molecular modelling showed that the points of enzyme attack were consistent with the stereospecificities of the enzymes, whereas the stereochemical courses of the cyclisation were solely governed by Baldwin's rules and did not invoke the involvements of a "cyclase".
Original language | English |
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Pages (from-to) | 1697-1704 |
Number of pages | 8 |
Journal | ChemBioChem |
Volume | 10 |
Issue number | 10 |
DOIs | |
Publication status | Published - 6 Jul 2009 |
Keywords
- Bis-epoxides
- Cascade reactions
- Enzyme models
- Epoxide hydrolases
- Hydrolases
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Organic Chemistry